This invention relates to the discovery that 4-aminopyridine and congeners or derivatives thereof are antagonists to drugs in animals and humans which act at or upon dopamine receptors or other neurotransmitter receptors. More specifically, this invention is the discovery that 4-aminopyridine and congeners or derivatives thereof are antagonists of butryophenones and congeners or derivatives thereof such as droperidol, haloperidol, azaperone, spiroperidol and lenperone. Additionally, 4-aminopyridine and congeners or derivatives thereof in combination with other drugs are antagonists of droperidol and fentanyl citrate (components of Innovar-Vet and Innovar) and xylazine hydrochloride (Rompun).
U.S. Pat. No. 3,928,589 discloses the treatment of humans afflicted with paralysis agitans by administration of 3,4-dihydroxyphenyl-1-alanine. U.S. Pat. No. 2,937,118 discloses compositions containing 4-methyl-2-amino-pyridine which are useful as a combined analgesic sympathomimetic. U.S. Pat. No. 2,460,710 discloses that 2-aminopyridine and its salts are effective agents for the control of organisms which cause decay of citrus fruits. U.S. Pat. No. 2,080,517 discloses that salts of organic acids with 2-6-diaminopyridine have bacteriostatic properties. The foregoing patents do not disclose the use of 4-aminopyridine.
4-Aminopyridine is an antagonist of ketamine-diazepam anesthesia in humans (Agoston, S., Salt, P. J., Erdmann, W., Hilkemeijer, T., Bencini, A., and Langrehr, D., J. Anaesth. 52, 367, 1980); however, the above referenced article suggests only that 4-aminopyridine is an antagonist to drugs which have a partial action on cholinergic receptors.
The present invention is a method of using an antagonist of a drug in animals and humans which act at or upon central nervous system receptors wherein the central nervous system receptors are selected from the group consisting of dopamine and other related catecholamine receptors and wherein the antagonist is selected from the group consisting of 4-aminopyridine, congeners of 4-aminopyridine, and derivatives of 4-aminopyridine.
It is an object of the present invention to use 4-aminopyridine and congeners or derivatives thereof as antagonists to drugs which act at or upon various receptors or synapses in the central nervous system, especially dopamine receptors or synapses.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof to reverse the depressant action of butyrophenones and congeners or derivatives thereof such as droperidol, haloperidol, azaperone, spiroperidol, and lenperone on the central nervous system by reducing the time of recovery, or by acting as an antidote to antagonize adverse reactions and/or by reversing the effects of toxic amounts of toxic dosages.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof in combination with naloxone hydrochloride, and congeners or derivatives thereof, an opiate antagonist, to completely reverse the pharmacologic actions of the mixture of droperidol and fentanyl citrate.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof as partial antagonists of xylazine hydrochloride (Rompun) and congeners or derivatives thereof and clonidine hydrochloride (Catapres) and their respective congeners or derivatives.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof in combination with yohimbine hydrochloride and congeners or derivatives thereof or piperoxan, which are .alpha.-2-adrenergic receptor blocking agents, to completely reverse or antagonize the pharmacologic actions of xylazine hydrochloride (Rompun) and congeners or derivatives thereof, a central .alpha.-2-adrenergic stimulant[s.], and of baclofen, phenothiazine tranquilizers, and congeners or derivatives and of acepromazine, and congeners or derivatives thereof.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof as antagonists of xylazine hydrochloride and congeners or derivatives thereof used in combination with atropine sulfate and congeners or derivatives thereof. It is a further object to use 4-aminopyridine and congeners or derivatives thereof in combination with yohimbine hydrochloride and congeners or derivatives thereof as antagonists of xylazine hydrochloride and congeners or derivatives thereof used in combination with sodium pentobarbital and congeners or derivatives thereof.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof in combination with yohimbine hydrochloride, piperoxan, or other adrenergic blocking agent and their respective congeners or derivatives in treatment of overdoses from clonidine hydrochloride (Catapres) and congeners or derivatives thereof.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof as antagonists for overdoses of butyrophenone agents used in treating psychiatric disorders.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof as partial or complete antagonists of phenothiazine [derivative] tranquilizers and congeners or derivatives thereof.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof as antagonists of acepromazine and congeners or derivatives thereof.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof as partial antagonists of althesin (Saffan, CT 1341) and congeners or derivatives thereof, a steroidal preparation containing two pregnanediones for the induction of anesthesia.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof as partial antagonists of central nervous system agents including but not limited to alcohol, ethanol, antihistamines, guaifenesin, barbiturates, inhalant anesthetics, hypnotic agents such as chloral hydrate, methaqualone, and central muscle relaxants such as methocarbamol and their respective congeners or derivatives.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof in combination with yohimbine hydrochloride and congeners or derivatives thereof to completely reverse or antagonize the pharmacologic actions of sodium pentobarbital, and congeners or derivatives of .alpha.-2-adrenergic stimulants.
It is a further object to use 4-aminopyridine and congeners or derivatives thereof in combination with other appropriate neurotransmitter antagonists affecting gamma-aminobutyric acid (GABA) receptors, glycine receptors, glutamate receptors, serotonin.sub.1 receptors, or serotonin.sub.2 receptors and their respective congeners or derivatives to completely antagonize the effects of central nervous system depressants.
These and other objects, aspects and advantages of this invention will become apparent from a consideration of the accompanying specification and claims.